The industrial grade enzymes which are used in machines, foods and drinks, textiles, leather, detergents, and various other applications are broadly divided into those obtained by extraction from animals and plants and those obtained as products of fermentation by microorganisms. Generally the enzymes of the former type are economically utilizable only to a limited extent because of limited sources of supply, whereas those of the latter type are extensively used because they have virtually infinite sources of supply and are producible relatively economically.
Generally the enzyme powders, no matter whether they originate in animals and plants or in microoganisms, which hawve been obtained by separation and purification are rarely put to use in their unaltered form. Most of these enzyme powders are granulated by themselves or in combination with an extender, a stabilizer, and other substances and put to use.
The granulated enzymes are generally in demand in particle sizes in the range of about 0.5 to 1.5 mm. Further, as in any other field, the granulated enzymes are required to be uniform in particle size, shape, and constituent makeup, rich in flowability, excellent in mechanical strength, and rigid enough to avoid sustaining cracking and chipping during storage or transportation. Besides these general requirements, the granulated enzymes must fulfill the following requirements.
It has been pointed out that enzymes, particularly proteases (proteolytic enzyme), may cause allergic reactions in some workers and users handling them when the dust of the enzymes comes in contact with the eyes, nose, and skin, for example. Therefore, as much as possible, it is necessary to prevent generation of dust during storage, transport, uses etc.
Mechanical strength and dust emission are not necessarily directly related. For example, some granules are so rigid as to offer fair resistance to disintegration and yet emit a fine dust and other granules are highly disintegrable into minute particles and yet are not reduced into a fine powder. Generally, the so-called elutriation method is used in the determination of the dust-emitting property of granulated enzymes. It is held that granulated enzymes are desirable when the amount of dust emitted thereby as determined by this method is not more than 150 GU/60 g (Ton den Ouden, Tenside Detergents, 14(1977) 4, P 209-210).
In virtually all cases, the granulated enzymes are put to use as dissolved in hot water or cold water. Particularly, in the case of granulated enzymes intended for use in detergents which form a main application for the industrial grade enzymes, from the point of the overall time consumed in laundering, these granulated enzymes must be capable of being quickly dispersed and dissolved to release the enzymes in water in a span of several minutes. Even if a granulated enzyme has high mechanical strength, therefore, it cannot be used as a good product if it possesses poor solubility in water. When an enzyme product having inferior storage stability is kept in storage for a long time, this enzyme product absorbs moisture and consequently swells and deforms, undergose disintegration and coalescence, suffers from loss of flowability and decline of activity, and sustains other forms of degeneration, to the extent of being deprived of its commercial value. The granulated enzymes, therefore, must possess sufficient solubility in water as described above and, on the other hand, absorb moisture only nominally and exhibit satisfactory moisture resistance.
Further, in the granulation of enzyme powder, there is entailed a peculiar important problem. Enzymes are generally liable to be inactivated by heat and water. In numerous cases, their inherent activity is impaired by the heat and water to which the enzymes are exposed during the course of granulation.
Therefore, it is important for granulation method of an enzyme powder to attain the granulation under conditions not capable of inactivating the enzyme, i.e. under conditions using a low temperature and a small amount of water sufficient to preclude the inactivation of enzyme.
Quite naturally, further, the operational conditions involved in the work of granulation such as, for example, length of the time required for the granulation, presence or absence of such mechanical troubles as adhesion of the raw material to the wall of the granulating machine, amount of such adjuvants as a binder to be used, and yield of the granulation (yield of acceptable product), viz. the conditions which may well be termed as economic factors, are equally important elements to be fulfilled.
Thus, the method adopted for the granulation of the enzyme powder can hardly be called satisfactory when it fails to fulfill all at once the numerous requirements mentioned above which, in a sense, turn out to be mutually incompatible requirements.
Various methods have been heretofore proposed as means for the granulation of enzyme powders. Substantially all of these methods, however, contemplate using water or an aqueous solution of a binder substance as the binder for the granules to be produced. Industrial grade enzymes, particularly those various enzymes which are obtained by the culture of microorganisms, generally contain impurities to a certain extent. These impurities manifest strong viscosity in the presence of water. When water is added to the raw material being granulated, therefore, it manifests its function as a binder. Since the binding force (binder property) of these impurities is variable with their composition, it is difficult to attain effective granulation of the enzyme powder under a fixed set of conditions, making it necessary to study the conditions for the granulation for each production lot of the enzyme powder. When the work of granulation is to be carried out in an automated operation, therefore, quality control of the product of this operation is difficult to obtain because the granulated enzyme acquires dispersed properties. A still more important problem arises from the fact that when an enzyme powder is granulated in the presence of water, the produced granules must be dried as by heating for expulsion of the water inevitably incorporated therein. Most emzymes be nature are relatively unstable and are liable to be inactivated in the presence of water. Thus, the presence of water itself can pose a problem. The subsequent exposure of the produced granules to the heat applied thereto for the purpose of drying aggravates the inactivation of an enzyme which inherently is rather unstable with respect to heat. Thus, the enzymatic activity is inevitably lost more or less during the course of the granulation.
Methods have been proposed for granulating enzyme powders in a non-aqueous medium using a waxy substance as a binder without the presence of water. The methods heretofore known to the art have a disadvantage that they require use of a third substance such as a core substance or fibrous substance during the work of granulation and necessitate provision of a complicated apparatus.
The method of Japanese Patent Pulbication SHO 46(1971)-4259, for example, effects the granulation of an enzyme powder by tumbling the raw material while using a viscous waxy substance such as a nonionic surfactant. Since this method requires to use a core substance, it produces granules with an insufficient enzyme content and further suffers from poor productivity.
Japanese Patent Publication SHO 52-47033 discloses a method which effects the granulation of an enzyme by preparing a liquid containing the enzyme and a wax as a binder, dispersing this liquid with centrifugal force, and cooling the dispersed drops of the liquid. This method does not permit a desired increase in the enzyme concentration in the produced granules because it requires use of the wax in an amount of at least 50% by weight based on the total amount of the materials for the granulation. It suffers from poor economy because the apparatus used therefor is voluminous and complicated.
Japanese Patent Publication SHO 58(1983)-26315 discloses a method for the granulation of an enzyme, which requires to use cellulosic fibers in an amount in the range of 2 to 40% by weight and a waxy substance and/or water as a granulating agent in an amount in the range of 50 to 70% by weight. This publicatgion discloses the granulation of alkalase by the use of a water-insoluble ethoxy aliphatic alcohol, as a working example using a waxy substance as a sole granulating agent. For this method, use of cellulosic fibers having an average length in the range of 50 to 160.mu. and an average width in the range of 20 to 30.mu. is an essential requirement. The addition of these cellulosic fibers is claimed to preclude deposition of an irremovable layer on the inner wall of the granulating machine and facilitate the control of the granulation. From the practical point of view, however, this method has a disadvantage in that the presence of such fibers requires the waxy substance to be used in a relatively large amount, elongates the time to be spent for the granulation, and aggravates the surface irregularity of produced granules and consequently enhances the generation of dust due to friction of granules.
In the granulation of an enzyme powder, efficiency of the work of granulation, shape and flowability of the produced granules, uniformity in the particle size, shape, and constituent makeup of the produced granules, generation of dust, rigidity, storage stability, solubility of the granules in water preparatory to actual use, and avoidance of the adverse effects exerted on the enzymatic properties by such additives as a binder are equally important considerations besides the problem of loss of activity during the course of granulation. Needless to say, economy constitutes another equally important consideration. The methods heretofore known to the art indeed possess some superior properties and exhibit improved qualities to some extent as described above. None of the conventional methods, however, can fulfill all the aforementioned considerations at once. All of them have some fault or other of their own.